O,S,S,-Trimethyl phosphorodithioate (OSS-Me), an impurity present in organophosphorus
insecticides, produced morphological alteration of rat and mouse terminal nonciliated bronchiolar epithelial (Clara) cells. The effects of OSS-Me on pulmonary and hepatic microsomal
enzymes were studied following its po administration to rats. Oral 28-day LD50 of OSS-Me for rats was 67 mg/kg. The animals were treated with OSS-Me at 40, 100, and 160 mg/kg and killed 24 hr later. The relative lung weights were not affected at this time. Pulmonary microsomal
benzo[a]pyrene hydroxylase decreased significantly; activities were less than 36% of control at the lowest dose. In contrast, the effect of OSS-Me treatment on hepatic
monooxygenase activity was moderate.
Benzo[a]pyrene hydroxylase,
p-nitroanisole demethylase, or
7-ethoxycoumarin deethylase were not affected by OSS-Me treatment at any dose. Pulmonary and hepatic
malathion carboxylesterase activities decreased following OSS-Me treatment. The decrease was more marked in liver. Time course effects of OSS-Me treatment on these parameters were examined by treating rats at 40 mg/kg, and the animals were killed at 6, 12, 24, and 72 hr
after treatment. The lung relative wet weight was increased markedly at 72 hr. The
benzo[a]pyrene hydroxylase activity of pulmonary microsomes was decreased at 24 and 72 hr
after treatment, the maximum decrease being observed at 72 hr. At this time,
glutathione of the lungs was depleted markedly. Significant decreases were not observed in hepatic
monooxygenase activities. Liver
glutathione content was not reduced at 72 hr. Pulmonary and hepatic
malathion carboxylesterase activities decreased throughout the time course. OSS-Me selectively inhibited
benzo[a]pyrene hydroxylase activity, depleted
glutathione, and caused morphological alteration of Clara cells in lungs of rats. Although the toxic mechanism(s) produced by OSS-Me remains unknown, these results support the view that the lung is a target organ of OSS-Me-induced delayed toxicity.